Content - SAKK 08/15

SAKK 08/15 PROMET – Can the diabetes medicine metformin also be used to treat prostate cancer?

In this study, we will investigate whether and to what extent metformin is effective, well tolerated and safe in combination with radiotherapy for patients with prostate cancer who have a recurrence after removal of the prostate gland. Up to now, patients in this situation are offered radiotherapy with or without hormonal treatment. We wish to find out whether the addition of metformin to the standard treatment can delay the progression of the disease and possibly help cure prostate cancer patients. To do so, the study participants will be divided into two groups: group A will be given radiotherapy in combination with metformin, and Group B will receive the same radiotherapy without the medication. The patients who are given metformin in addition to radiotherapy will be chosen at random. This study will be conducted at in more than 20 hospitals in Switzerland, Germany and France.

Metformin is a well-known and widely prescribed medication taken in tablet form by patients with diabetes to control the blood levels of glucose (sugar). Several studies have shown that metformin can potentially halt the growth of tumour cells as well as increase the efficacy of the radiation treatment. However, as not enough is known about the efficacy of combining radiotherapy and metformin for patients with prostate cancer who have a recurrence after removal of the prostate gland, the study will investigate this question.

Study Chair

Dr. Alan Dal Pra, Inselspital, Bern, +41 31 632 26 32

  • Contacts at the hospitals

  • Inclusion Criteria

    • Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
    • Histologically confirmed adenocarcinoma of the prostate without small cell features
    • Tumor stage pT2a-3b, pN0 or cN0, M0, R0-1 resection margins, according to UICC TNM 2009, Gleason score available
    • Radical prostatectomy (RP) at least 12 weeks before registration
    • PSA progression after RP defined as two consecutive rises with the final PSA > 0.1 ng/mL or three consecutive rises. The first value must be measured earliest 4 weeks after RP
    • PSA ≤ 2 ng/mL within 14 days prior to registration
    • Age ≥ 18 years at time of registration
    • WHO performance status 0-1
    • Adequate hepatic function within 14 days prior to registration: bilirubin ≤ 1.5 x ULN (exception if Gilbert's syndrome ≤ 3 x ULN), AST and ALT ≤ 2.5 x ULN
    • Adequate renal function within 14 days prior to registration: calculated corrected creatinine clearance ≥ 60 mL/min, according to the formula of corrected Cockcroft-Gault
    • Patient agrees not to father a child during trial treatment and during 6 months thereafter
  • Exclusion Criteria

    • Persistent PSA (> 0.4 ng/mL) 4 to 20 weeks after RP
    • Pelvic lymph node enlargement > 0.8 cm in short axis diameter (cN positive) assessed by mpMRI within 12 weeks prior to registration, unless the enlarged lymph node is sampled and negative
    • Evidence of macroscopic local recurrence assessed by mpMRI within 12 weeks prior to registration
    • Palpable prostatic fossa mass suggestive of recurrence, unless an ultrasound guided biopsy is negative for malignancy
    • Presence or history of prostate cancer metastases. In case of clinical suspicion (e.g. bone pain), imaging (e.g. bone scan, Cholin-PET, PSMA-PET, whole body MRI) must be performed. The imaging method is at the discretion of the investigator.
    • History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of curatively treated localized non-melanoma skin cancer
    • Patients on pharmacotherapy for diabetes mellitus
    • Treatment with metformin within the last 3 months prior to registration
    • Prior pelvic radiotherapy
    • Hormonal treatment as bilateral orchiectomy prior or following RP
    • Usage of products known to affect PSA levels within 4 weeks prior to start of trial treatment
    • Bilateral hip prosthesis
    • Severe or active co-morbidity likely to impact on the advisability of salvage RT, e.g.:
      • History of inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
      • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
      • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
      • Transmural myocardial infarction within the last 6 months
      • Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Any condition associated with increased risk of lactic acidosis (e.g. alcohol abuse, congestive heart failure NYHA III or IV
    • Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including viral or other hepatitis, current alcohol abuse, or cirrhosis
    • Severe or uncontrolled kidney disease resulted in impaired kidney function (GFR <60ml/min)
    • Any acute or chronic condition that could cause tissue hypoxia (e.g. cardiac or respiratory insufficiency, recent myocardial infarction, shock)
    • Treatment with any experimental drug or participation within a clinical trial within 30 days prior to registration (exception: concurrent participation in the biobank project SAKK 63/12 is allowed)
    • Any concomitant drug contraindicated for use with metformin according to the approved product information
    • Known hypersensitivity to metformin/placebo or to any of its components
    • Hereditary intolerance to fructose; known galactose-1-phosphate uridyl transferase deficiency, UDP galactose 4 epimerase deficiency, galactokinase deficiency, Fanconi-Bickel syndrome, congenital lactase deficiency, or glucose-galactose malabsorption (due to the lactose-containing placebo)
    • Inability or unwillingness to swallow oral medication
    • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications

Locations for this trial:

Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Inselspital
Freiburgstrasse 8
3010 Bern
Radio-Onkologiezentrum Biel–Seeland–Berner Jura AG
Rebenweg 38
0 2503 Biel-Bienne
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Radio-Onkologie Solothurn AG
Schöngrünstrasse 42
0 4500 Solothurn
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Radio-Onkologie Berner Oberland AG
Krankenhausstrasse 12
0 3600 Thun
Klinik Hirslanden Zürich
Witellikerstrasse 40
0 8032 Zürich